ADIRF Suppresses Tumor Progression And Involves Keratinocyte Differentiation In Esophageal Squamous Cell Carcinoma

Background: and Aim: Adipogenesis regulatory factor (ADIRF) regulates fat cell development and promotes adipogenic differentiation, but the role in esophageal squamous cell carcinoma (ESCC) is unknow. We aimed to interpret the regulatory effects of ADIRF in the progression and differentiation of ESCC. Methods: : The expression ADIRF was evaluated in the RNA-seq dataset and the immunohistochemically examined in the ESCC tissues. The associations with the clinical features were studied in an ESCC cohort. The effect on ESCC cells growth and migration were assessed. The core functions of ADIRF were analyzed according to the co-expressed genes. Results: : The expression of ADIRF was decreased in cancerous mucosa and significantly downregulated in the advanced ESCCs. The immunostainings of ADIRF were reversely correlated with the progressing of AJCC stage ( r =-0.41) and tumor stage ( r =-0.56) in the carcinomas. The high expression of ADIRF was capable to indicated the patients without deep invasion (AUC=0.805, P<0.001). In multiple ESCC cells, ADIRF overexpression obviously suppressed the cell proliferation, migration and division. According to assessing the core functions of co-expressed genes, the ADIRF was putatively associated with the keratinocyte differentiation. Among the keratinocyte differentiation associated genes, SPRR1A, SPRR1B, PKP3, SPRR2D, and FLG were detected to independently correlate with the ESCC prognosis. Thereinto, SPRR1A was with the minimum hazard ratio (HR=0.11, 95%CI: 0.02-0.62) and significantly downregulated in the advanced ESCCs. Conclusions: : ADIRF might suppress the tumor progression and be speculated to regulate esophageal keratinocyte differentiation during the development of ESCC.